软X射线发光纳米探针在生物医学分析中的应用研究

Development of a novel luminescent nanoprobe is greatly significant in the.biological applications of early diagnosis for highly-sensitive detection of tumor biomarkers and biomedical imaging analysis. In this proposal, we aim to develop a new analytical technology by using soft X-ray luminescent nanocrystals as a novel bioprobe. In this regard, we will develop a novel method for immunoassays of tumor biomarkers with high sensitivity and low fluorescence background, and we will also provide a new strategy of in vivo luminescence bio-imaging with an excellent penetrability. To this end, we will design and synthesis a kind of soft X-ray luminescence nanoprobes with high luminescence efficiency by rational selection of rare-earth ions as host and luminescence center in nanocstystals, as well as optimization of doping concentrations and core-shell structures to induce energy quenching and improve luminescence intensity. In addition, this study will develop a novel analytical method for tumor biomarker immunoassays based on soft X-ray luminescence nanoprobes, allowing the highly sensitive analysis without fluorescence background and enhanced signal to noise ratio. Meanwhile, the soft X-ray luminescence nanobioprobe will be employed to develop a strategy for in vivo biomedical imaging of tissue or organ in the depth, which will overcome the drawbacks of low penetrability in the current technique of bioimaging using Vis-NIR light source. Therefore, we envision that the soft X-ray luminescence nanoprobe will show great promising in the biomedical Analysis.

新型发光纳米探针在肿瘤标志物高灵敏检测和生物医学成像分析等重大疾病早期诊断中的应用具有重大的研究意义。本研究项目拟发展一种基于软X射线发光纳米晶体为生物探针的分析新技术，旨在构建高灵敏无荧光背景的疾病标志物免疫分析新方法以及较深穿透能力的活体组织发光成像分析的新策略。以此为目标，研究将设计与合成一类具有较高发光效率的软X射线发光纳米探针，合理选取稀土离子作为纳米基质和发光中心，优化所掺杂的稀土离子浓度并设计核壳结构以减少能量淬灭并提高发光强度。构建基于软X射线发光纳米探针的肿瘤疾病标志物免疫分析新方法，实现无荧光背景的高灵敏分析检测，以及提高分析检测信噪比。同时，采用软X射线发光纳米生物探针以发展一种对活体组织器官具有较深穿透能力的生物医学发光成像分析方法，克服目前采用可见光-近红外光为光源的活体发光成像分析中穿透性不足的缺点。因此，软X射线发光纳米探针在生物医学分析中具有较强的应用前景。

本项目按照项目任务书，开展了软X射线发光纳米探针的构建及其在生物医学分析中的研究应用。取得的主要研究成果如下：（1）以新型稀土氟化物纳米闪烁体材料的制备、辐射发光性能表征、发光机理探究为研究基础，开发了一系列癌症标志物的新型无背景体外检测分析手段；（2）利用DNA滚环扩增技术制备多价DNA空间网络，实现对循环肿瘤细胞的富集和分离。本项目发表SCI收录期刊论文4篇，包括Anal. Chem.、Chem. Commun.、J. Chromatogr. A、高等学校化学学报。